Severe irAEs With Ipilimumab For Metastatic Melanoma May Not Recur On PD-1 Inhibitor Therapy

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Patients who experience severe immune-related adverse events (irAEs) during ipilimumab therapy for metastatic melanoma may not develop the same toxicities during subsequent PD-1 inhibitor treatment, suggest French researchers. 

The 56 patients in the cohort study had all developed at least one grade 3 or 4 irAE in response to a median three cycles of ipilimumab, while 23% had two and 4% had three concomitant irAEs. The most common types of irAEs were gastrointestinal (47%) and endocrine (23%). 

After a median 25-week wash-out period, all the irAEs had resolved before the patients went on to receive a median 12 cycles of pembrolizumab 2 mg/kg or nivolumab 3 mg/kg, say Angélique Brunot, from the Comprehensive Cancer Center Eugéne Marquis in Rennes, and co-workers. 

Overall, 36% of patients experienced 23 irAEs in response to PD-1 inhibitor therapy after a median 49 days of treatment, most commonly endocrine (11%), pulmonary (9%), gastrointestinal (7%) and cutaneous (7%) side effects. Grade 3 irAEs occurred in 18% and grade 4 in 4%. 

One patient was given anti-TNF therapy for grade 4 colitis and over half were given systemic corticosteroids (58%) or endocrine therapy (50%), while 9% required a treatment break. There were no grade 5 irAEs. 

An objective response to PD-1 inhibitor therapy was achieved by 43% of patients, including complete responses in 18% and a partial response in 25%. Median overall survival was 21 months, with 29% of the cohort continuing treatment at time of analysis. 

Of note, patients who had previously responded to ipilimumab were significantly more likely to respond to PD-1 inhibitor therapy than those who had not (88 vs 35%) but there was no significant relationship between response to treatment and occurrence of irAEs. 

“Although our study population is one of the largest cohorts on the topic, the small size of the study population does not allow a high precision in estimation”, the researchers admit.

Nevertheless, they conclude in JAMA Dermatology: “The findings suggest that anti–PD-1 therapy may be associated with reduced risk of toxic effects and improved survival among patients who have experienced severe toxic effects associated with ipilimumab therapy.

“In addition, response to anti–PD-1 therapy appears to be favorable.” 

Reference 

Brunot A, Grob J-J, Jeudy G, et al. Association of anti-programmed cell death 1 antibody treatment with risk of recurrence of toxic effects after immune-related adverse events of ipilimumab in patients with metastatic melanoma. JAMA Derm; Advance online publication 15 July 2020. doi:10.1001/jamadermatol.2020.2149